In this project, we will use newly developed computational methods to address outstanding issues in bacterial chemotaxis. These include the question of how bacteria navigate through complex natural environments; how the flexible tethers associated with the chemotaxis receptors influence adaptation; and whether signaling proteins move between the cytoplasm and the membrane in response to chemotactic stimulation. We propose to tackle these and related issues by existing computational methods already formulated by our group as well as novel programs that we will write for the purpose. We will test and refine our theoretical results experimentally through collaborations with established investigators. Our work will advance the understanding of this bacterial chemotaxis, which has been shown to play a crucial role in the invasiveness of pathogenic bacteria and the formation of biofilms in clinical and industrial settings. From a broader perspective, our work will contribute to the general understanding of signal transduction pathways in both bacterial and eucaryotic cells. Because the chemotaxis pathway of coliform bacteria is so well studied, we have an opportunity to probe it in greater depth than is possible in other cell types. We can therefore address fundamental issues such as the integrative interaction of contiguous components of the pathway, and the constraints imposed by diffusive movements through the cytoplasm. Moreover, the intimate involvement of computational and experimental approaches in our study will both contribute to, and derive benefit from, the raidly expanding area of systems biology. [unreadable] [unreadable]